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The mesenchymal-to-epithelial transition (MET) gene is altered and becomes a driver mutation in up to 5% of non-small-cell lung cancer (NSCLC). We report our institutional experience treating patients with MET exon 14 skipping (METex14) mutations, including responses to the MET inhibitors crizotinib and cabozantinib. We identified cases of NSCLC with METex14 mutations using an institutionally developed or commercial next-generation sequencing assay. We assessed patient and disease characteristics by retrospective chart review. Some patients were treated off-label by the physician with crizotinib or cabozantinib, and tumor responses to these agents were assessed. A total of 15 patients with METex14-mutated NSCLC were identified, predominantly male (n=10) with a smoking history (60%) and a median age of 74.0 years. No other actionable somatic mutations were detected. Stage distribution included 26.7% stage I, 6.7% stage II, 6.7% stage III, and 60.0% stage IV. Among patients treated with crizotinib or cabozantinib (n=6), three patients showed partial response and one patient showed stable disease on the basis of RECIST criteria. Four patients experienced side effects requiring drug holiday, reduction, or cessation. Our findings highlight the diversity in presentation and histology of NSCLC with METex14 mutations, which were found in the absence of other actionable driver mutations. We observed evidence of tumor response to crizotinib and cabozantinib, supporting the previous reports that METex14 mutations in NSCLC are actionable driver events.
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Adenocarcinoma del Pulmón/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Exones , Neoplasias Pulmonares/patología , Mutación , Proteínas Proto-Oncogénicas c-met/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Anciano , Anciano de 80 o más Años , Anilidas/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Crizotinib/administración & dosificación , Transición Epitelial-Mesenquimal , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Piridinas/administración & dosificación , Estudios RetrospectivosRESUMEN
Perfusion processes typically require removal of a continuous or semi-continuous volume of cell culture in order to maintain a desired target cell density. For fast growing cell lines, the product loss from this stream can be upwards of 35%, significantly reducing the overall process yield. As volume removed is directly proportional to cell growth, the ability to modulate growth during perfusion cell culture production thus becomes crucial. Leveraging existing media components to achieve such control without introducing additional supplements is most desirable because it decreases process complexity and eliminates safety and clearance concerns. Here, the impact of extracellular concentrations of sodium (Na) and potassium (K) on cell growth and productivity is explored. High throughput small-scale models of perfusion revealed Na:K ratios below 1 can significantly suppress cell growth by inducing cell cycle arrest in the G0/1 phase. A concomitant increase in cell specific productivity was also observed, reaching as high as 115 pg/cell/day for one cell line studied. Multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrated similar responses to lower Na:K media, indicating the universal applicability of such an approach. Product quality attributes were also assessed and revealed that effects were cell line specific, and can be acceptable or manageable depending on the phase of the drug development. Drastically altering Na and K levels in perfusion media as a lever to impact cell growth and productivity is proposed.
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Técnicas de Cultivo Celular por Lotes , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cloruro de Potasio/farmacología , Cloruro de Sodio/farmacología , Animales , Reactores Biológicos , Células CHO , Recuento de Células , Puntos de Control del Ciclo Celular/efectos de los fármacos , Cricetulus , Medios de Cultivo/farmacologíaRESUMEN
Detection of microbial products by host inflammasomes is an important mechanism of innate immune surveillance. Inflammasomes activate the caspase-1 (CASP1) protease, which processes the cytokines interleukin (IL)-1ß and IL-18, and initiates a lytic host cell death called pyroptosis. To identify novel CASP1 functions in vivo, we devised a strategy for cytosolic delivery of bacterial flagellin, a specific ligand for the NAIP5 (NLR family, apoptosis inhibitory protein 5)/NLRC4 (NLR family, CARD-domain-containing 4) inflammasome. Here we show that systemic inflammasome activation by flagellin leads to a loss of vascular fluid into the intestine and peritoneal cavity, resulting in rapid (less than 30 min) death in mice. This unexpected response depends on the inflammasome components NAIP5, NLRC4 and CASP1, but is independent of the production of IL-1ß or IL-18. Instead, inflammasome activation results, within minutes, in an 'eicosanoid storm'--a pathological release of signalling lipids, including prostaglandins and leukotrienes, that rapidly initiate inflammation and vascular fluid loss. Mice deficient in cyclooxygenase-1, a critical enzyme in prostaglandin biosynthesis, are resistant to these rapid pathological effects of systemic inflammasome activation by either flagellin or anthrax lethal toxin. Inflammasome-dependent biosynthesis of eicosanoids is mediated by the activation of cytosolic phospholipase A(2) in resident peritoneal macrophages, which are specifically primed for the production of eicosanoids by high expression of eicosanoid biosynthetic enzymes. Our results therefore identify eicosanoids as a previously unrecognized cell-type-specific signalling output of the inflammasome with marked physiological consequences in vivo.
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Eicosanoides/biosíntesis , Inflamasomas/metabolismo , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/genética , Antígenos Bacterianos/metabolismo , Proteínas Reguladoras de la Apoptosis/deficiencia , Proteínas Reguladoras de la Apoptosis/metabolismo , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Líquidos Corporales/metabolismo , Temperatura Corporal , Señalización del Calcio , Proteínas de Unión al Calcio/deficiencia , Proteínas de Unión al Calcio/metabolismo , Permeabilidad Capilar , Caspasa 1/deficiencia , Caspasa 1/metabolismo , Ciclooxigenasa 1/deficiencia , Citosol/metabolismo , Muerte , Eicosanoides/metabolismo , Femenino , Flagelina/genética , Flagelina/inmunología , Flagelina/metabolismo , Transferencias de Fluidos Corporales , Hematócrito , Inmunidad Innata/inmunología , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Interleucina-18 , Interleucina-1beta , Mucosa Intestinal/metabolismo , Legionella pneumophila , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Inhibidora de la Apoptosis Neuronal/deficiencia , Proteína Inhibidora de la Apoptosis Neuronal/metabolismo , Cavidad Peritoneal , Lavado Peritoneal , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Infecciones por Salmonella/inmunología , Salmonella typhimurium/inmunología , Factores de TiempoRESUMEN
PURPOSE: 5-Fluorouracil (5-FU) has been well described for a failing trabeculectomy bleb, but not for aqueous shunts. We sought to determine whether subconjunctival 5-FU prolongs the intraocular pressure (IOP) efficacy of Ahmed shunts. METHODS: We included all patients with Ahmed FP-7 implantation by one surgeon at Yale University. Patients with <3 months follow-up were excluded. Injections were done on a case-by-case basis, usually for IOP > 21 on >2 medications. Five-milligram (0.1 cc) injections were made over the plate. The control group consisted of Ahmed FP-7 patients without injections. The main outcome measure was IOP. Secondary outcome was success (IOP <21 mmHg, 20% decrease from preoperative IOP, and no reoperation). RESULTS: The average age of controls was 72.5 ± 16.6 years, and 63.7 ± 18.8 with 5-FU (p = 0.02). Forty-four patients received 5-FU and 45 did not. Mean preoperative IOP in controls was 31.5 ± 11 mmHg on 3.1 ± 1 medications, and 31.9 ± 9.0 mmHg (p = 0.86) on 3.3 ± 0.9 medications with 5-FU (p = 0.18). At a mean 137 days after surgery, mean pre-injection IOP was 25.3 ± 7.7 mmHg on 2.0 ± 1.3 medications. Five years following implantation, control IOPs averaged 12.9 ± 7.1 mmHg (53% decrease from preoperative IOP, p < 0.001) on 1.4 ± 1.1 medications versus 17.2 ± 4.9 mmHg (46% decrease from preoperative, 32% decrease from pre-5FU IOP, p < 0.001) on 2.7 ± 0.8 medications with 5-FU. The IOP at 5 years was statistically similar in both groups (p = 0.23). Five-year success rates trended higher with 5-FU (77 vs. 67%, p = 0.38). CONCLUSIONS: Subconjunctival injection of 5-FU sustained a significant long-term decline in intraocular pressures in eyes with failing Ahmed shunts. Outcomes between eyes receiving injections and controls were statistically similar.
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Fluorouracilo/administración & dosificación , Implantes de Drenaje de Glaucoma/efectos adversos , Glaucoma/cirugía , Presión Intraocular/efectos de los fármacos , Cuidados Posoperatorios/métodos , Anciano , Conjuntiva , Femenino , Estudios de Seguimiento , Glaucoma/tratamiento farmacológico , Glaucoma/fisiopatología , Humanos , Inmunosupresores/administración & dosificación , Inyecciones , Masculino , Persona de Mediana Edad , Falla de Prótesis , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Nearly 3,000 Australians tragically end their lives by suicide each year, underscoring a major national public health challenge with substantial socio-economic ramifications. Australia's National Mental Health Plans (NMHPs) aim to improve mental health and reduce suicide rates. This study investigates their effectiveness by analyzing how age-standardized suicide rates across Australian jurisdictions have fluctuated alongside the implementation of five NMHPs from 1987 to 2021. Findings reveal mixed impacts, with some plans linked to decreases and others associated with increases in suicide rates across different periods and regions. Notably, the recent decline in 2020 requires careful consideration amidst COVID-19 pandemic influences. These insights not only provide valuable evidence for shaping future mental health policies and initiatives but also for future health services research.
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Pueblos de Australasia , Salud Mental , Suicidio , Humanos , Australia/epidemiología , Reforma de la Atención de Salud , PandemiasRESUMEN
Background: Patients with serious illness benefit from conversations to share prognosis and explore goals and values. To address this, we implemented Ariadne Labs' Serious Illness Care Program (SICP) at Stanford Health Care. Objective: Improve quantity, timing, and quality of serious illness conversations. Methods: Initial implementation followed Ariadne Labs' SICP framework. We later incorporated a team-based approach that included nonphysician care team members. Outcomes included number of patients with documented conversations according to clinician role and practice location. Machine learning algorithms were used in some settings to identify eligible patients. Results: Ambulatory oncology and hospital medicine were our largest implementation sites, engaging 4707 and 642 unique patients in conversations, respectively. Clinicians across eight disciplines engaged in these conversations. Identified barriers that included leadership engagement, complex workflows, and patient identification. Conclusion: Several factors contributed to successful SICP implementation across clinical sites: innovative clinical workflows, machine learning based predictive algorithms, and nonphysician care team member engagement.
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Cuidados Críticos , Enfermedad Crítica , Humanos , Enfermedad Crítica/terapia , Comunicación , Relaciones Médico-Paciente , Centros Médicos AcadémicosRESUMEN
Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening complication of the administration of PN. The development of PNALD may be partly due to the composition of the lipid emulsion administered with PN: soybean oil-based lipid emulsions (SOLE) are associated with liver disease, while fish oil-based lipid emulsions (FOLE) are associated with prevention and improvement of liver disease. The objective of this study was to determine how the choice of lipid emulsion modified the production of bioactive lipid mediators (LMs). We utilized a mouse model of steatosis to study the differential effect of FOLE and SOLE. We subsequently validated these results in serum samples from a small cohort of human infants transitioning from SOLE to FOLE. In mice, FOLE was associated with production of anti-inflammatory, proresolving LMs; SOLE was associated with increased production of inflammatory LMs. In human infants, the transition from SOLE to FOLE was associated with a shift toward a proresolving lipidome. Together, these results demonstrate that the composition of the lipid emulsion directly modifies inflammatory homeostasis.
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Ácidos Grasos Omega-3/farmacología , Hígado Graso/tratamiento farmacológico , Mediadores de Inflamación/metabolismo , Administración Oral , Animales , Emulsiones , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/uso terapéutico , Hígado Graso/sangre , Hígado Graso/metabolismo , Femenino , Humanos , Lactante , Inyecciones Intravenosas , Masculino , Ratones , Aceite de Soja/administración & dosificación , Aceite de Soja/farmacología , Aceite de Soja/uso terapéuticoRESUMEN
Estrogen receptors (ERs) are expressed in leukocytes and in every ocular tissue. However, sex-specific differences and the role of estradiol in ocular inflammatory-reparative responses are not well understood. We found that female mice exhibited delayed corneal epithelial wound closure and attenuated polymorphonuclear (PMN) leukocyte responses, a phenotype recapitulated by estradiol treatment both in vivo (topically in male mice) and in vitro (corneal epithelial cell wound healing). The cornea expresses 15-lipoxygenase (15-LOX) and receptors for lipoxin A(4) (LXA(4)), which have been implicated in an intrinsic lipid circuit that regulates corneal inflammation and wound healing. Delayed epithelial wound healing correlated with lower expression of 15-LOX in the regenerated epithelium of female mice. Estradiol in vitro and in vivo down-regulated epithelial 15-LOX expression and LXA(4) formation, while estradiol abrogation of epithelial wound healing was completely reversed by treatment with LXA(4). More important, ERß and ERα selectively regulated epithelial wound healing, PMN cell recruitment, and activity of the intrinsic 15-LOX/LXA(4) circuit. Our results demonstrate for the first time a sex-specific difference in the corneal reparative response, which is mediated by ERß and ERα selective regulation of the epithelial and PMN 15-LOX/LXA(4) circuit. These findings may provide novel insights into the etiology of sex-specific ocular inflammatory diseases.
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Córnea/efectos de los fármacos , Córnea/patología , Epitelio Corneal/efectos de los fármacos , Epitelio Corneal/patología , Estrógenos/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Araquidonato 15-Lipooxigenasa/metabolismo , Línea Celular , Córnea/citología , Córnea/fisiología , Epitelio Corneal/citología , Epitelio Corneal/fisiología , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Femenino , Humanos , Leucocitos/citología , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Receptores de Formil Péptido/metabolismo , Caracteres Sexuales , Cicatrización de Heridas/fisiologíaRESUMEN
Dismantling racism in health care demands that medical education promote racial justice throughout all stages of medical training. However, racial bias can be fostered unintentionally, influencing the way we make decisions as clinicians with downstream effects on patient health and health equity. The development of any anti-racism curriculum in medicine requires the ability to identify racial bias in practices we have not previously recognized as explicitly racist or unjust. This has limited the creation and delivery of effective anti-racism education in health care.
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Educación Médica , Racismo , Humanos , Antiracismo , Atención a la Salud , Justicia SocialRESUMEN
Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 in Shank3B knockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype and Shank3B knockout mice. However, activation of the CA2 enhanced vCA1 theta power in Shank3B knockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function.
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Trastorno del Espectro Autista , Ratones , Animales , Ratones Noqueados , Trastorno del Espectro Autista/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Deleción Cromosómica , Discriminación Social , Proteínas de Microfilamentos/genéticaRESUMEN
Background: In patients with multiple myeloma, thrombotic microangiopathy is a rare adverse event associated with proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib. Case Presentation: Two patients with multiple myeloma who presented with carfilzomib-induced thrombotic microangiopathy received eculizumab with subsequent stabilization of renal function. Conclusions: Given the overall rarity of this adverse event, the simultaneous presentation of these 2 cases was unexpected. These cases underscores the need for heightened awareness in clinical practice of thrombotic microangiopathy. The potential role of eculizumab as a therapeutic treatment in the setting of thrombotic microangiopathy requires further investigation.
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Multiple reporting guidelines for artificial intelligence (AI) models in healthcare recommend that models be audited for reliability and fairness. However, there is a gap of operational guidance for performing reliability and fairness audits in practice. Following guideline recommendations, we conducted a reliability audit of two models based on model performance and calibration as well as a fairness audit based on summary statistics, subgroup performance and subgroup calibration. We assessed the Epic End-of-Life (EOL) Index model and an internally developed Stanford Hospital Medicine (HM) Advance Care Planning (ACP) model in 3 practice settings: Primary Care, Inpatient Oncology and Hospital Medicine, using clinicians' answers to the surprise question ("Would you be surprised if [patient X] passed away in [Y years]?") as a surrogate outcome. For performance, the models had positive predictive value (PPV) at or above 0.76 in all settings. In Hospital Medicine and Inpatient Oncology, the Stanford HM ACP model had higher sensitivity (0.69, 0.89 respectively) than the EOL model (0.20, 0.27), and better calibration (O/E 1.5, 1.7) than the EOL model (O/E 2.5, 3.0). The Epic EOL model flagged fewer patients (11%, 21% respectively) than the Stanford HM ACP model (38%, 75%). There were no differences in performance and calibration by sex. Both models had lower sensitivity in Hispanic/Latino male patients with Race listed as "Other." 10 clinicians were surveyed after a presentation summarizing the audit. 10/10 reported that summary statistics, overall performance, and subgroup performance would affect their decision to use the model to guide care; 9/10 said the same for overall and subgroup calibration. The most commonly identified barriers for routinely conducting such reliability and fairness audits were poor demographic data quality and lack of data access. This audit required 115 person-hours across 8-10 months. Our recommendations for performing reliability and fairness audits include verifying data validity, analyzing model performance on intersectional subgroups, and collecting clinician-patient linkages as necessary for label generation by clinicians. Those responsible for AI models should require such audits before model deployment and mediate between model auditors and impacted stakeholders.
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Memory is a binary process relying on a short-term form lasting minutes to forge and communicate with a long-term form lasting years. Yale's Bicentennial Symposium opened with a lecture elucidating the obscure process of long-term memory formation. From his decades of research, Nobel Laureate Eric Kandel offered insight into the molecular framework that is long term-memory.
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Memoria a Largo Plazo , Premio NobelRESUMEN
Assisted reproductive technology (ART) has been recognized for its success in treating infertility, a condition that affects 15 percent of couples in the United States. The most popular option is in vitro fertilization (IVF), which relies on embryo culture, selection, and transfer for implantation, with the ultimate aim of pregnancy. Previous embryo selection methods relied on morphological factors to select for greatest viability. At Yale's Frontiers in Reproduction Conference on April 29, 2011, at the New Haven Lawn Club, Dr. Denny Sakkas of Yale's Department of Obstetrics, Gynecology, and Reproductive Sciences presented a paradigm shift: using morphological factors along with metabolic, protein, and genetic markers in culture media to enhance embryo selection and IVF success rates.
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Transferencia de Embrión/tendencias , Fertilización In Vitro/tendencias , Reproducción/fisiología , Femenino , Genómica , Humanos , Metabolómica , EmbarazoRESUMEN
A 56-year-old Hispanic man with a history of disseminated coccidioidomycosis was diagnosed with persistent glucocorticoid insufficiency and pseudohyperaldosteronism secondary to posaconazole toxicity. This case was notable for unexpected laboratory findings of both pseudohyperaldosteronism and severe glucocorticoid deficiency due to posaconazole's mechanism of action on the adrenal steroid synthesis pathway. Transitioning to fluconazole and starting hydrocortisone resolved the hypokalemia but not his glucocorticoid deficiency. This case highlights the importance of recognizing iatrogenic glucocorticoid deficiency with azole antifungal agents and potential long term sequalae.
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Tangential flow filtration (TFF) and alternating tangential flow (ATF) filtration technologies using hollow fiber membranes are commonly utilized in perfusion cell culture for the production of monoclonal antibodies; however, product retention remains a known and common problem with these systems. To address this issue, commercially available hollow fibers ranging from several hundred kilo-Daltons (kDa) to 0.65 µm in nominal pore size are tested and are all demonstrated to undergo moderate to severe product retention. Further investigation revealed accumulation of particles in the same size range (≈20-200 nm) as the pores. Based on the assumption that these particles contribute to product retention and membrane plugging, a hollow fiber with an unconventionally larger pore size is subsequently identified and demonstrated to drastically reduce product retention with no impact to cell clarification. Furthermore, these hollow fibers demonstrate surprisingly high membrane capacities, making them an attractive solution to the problem of product retention in perfusion reactors.
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Técnicas de Cultivo Celular por Lotes/métodos , Reactores Biológicos , Filtración/instrumentación , Membranas Artificiales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/química , Técnicas de Cultivo Celular por Lotes/instrumentación , Biofarmacia/instrumentación , Tamaño de la PartículaRESUMEN
Background Urinary tract infections (UTIs) are among the most common bacterial infections. Options for initial treatment of pyelonephritis or UTI requiring hospitalization include levofloxacin (LVF) or extended-spectrum cephalosporins. Globally, uropathogenic Escherichia coli resistance rates to fluoroquinolones have increased in recent years. Objective To compare clinical outcomes of patients receiving ceftriaxone (CTX) to those who received LVF empirically for the treatment of E. coli UTI. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective, single center, cohort study of adults with a urine culture positive for E. coli who received either IV LVF or CTX empirically for the treatment of UTI. Main outcome measure The primary outcome was hospital length of stay. Secondary outcomes include time to susceptible therapy (TsT), hospital cost, and susceptibility to empiric therapy. Results There was no statistically significant difference in LOS or hospital cost. Subgroup analysis compared patients that received concordant CTX treatment and patients that received discordant LVF treatment. Patients that received concordant CTX treatment had a nonsignificant shorter median LOS (4.16 vs. 6.34 days). Median hospital cost was lower ($4345 vs. $8462, p = 0.004) and median TsT was shorter (5.83 vs. 64.46 h, p < 0.001) in the concordant CTX group. Conclusion Choice of empiric antibiotic therapy should be based on local antibiogram data. For patients with UTI requiring hospitalization, CTX seems to be an effective empiric therapy for most patients. More data is required to examine the effectiveness of local and source specific antibiograms on clinical outcomes when guiding treatment of patients with UTI.
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Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Levofloxacino/uso terapéutico , Infecciones Urinarias/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Ceftriaxona/farmacología , Estudios de Cohortes , Infecciones por Escherichia coli/diagnóstico , Femenino , Humanos , Levofloxacino/farmacología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones Urinarias/diagnósticoRESUMEN
When a patient is found to have multiple lung tumors, distinguishing whether they represent metastatic nodules or separate primary cancers is crucial for staging and therapy. We report the case of a 79-year-old patient with two surgically resected synchronous left upper lobe adenocarcinomas initially pathologically staged as T3 (IIB), indicating adjuvant chemotherapy should be recommended. However, the tumors appeared radiographically distinct, so next-generation sequencing was performed on each nodule. Each tumor harbored a different mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation, an emerging targetable mutation, suggestive of distinct clonality. While the in frame protein deletion was the same in each tumor, the nucleotide base substitutions were different. Thus, the patient was down-staged to having two separate IA tumors, spared of adjuvant chemotherapy, and routine surveillance was recommended. This case highlights the utility of using molecular analysis in diagnosing and treating multifocal lung tumors, and the process of convergent molecular evolution toward a common oncogenic driver mutation. This is the first case of multiple synchronous lung tumors each harboring a distinct MET exon 14 splice site mutation.